BisCEET: A Visual Browser for Biosynthetic Gene Clusters Aiding in the Identification of Natural Product Variants and Distinct Tailoring Enzymes.

Genes involved in the biosynthesis of microbial natural products (NPs) are typically arranged in biosynthetic gene clusters (BGCs). Different congeners of an NP family typically possess distinct chemical features introduced by additional tailoring enzymes encoded in the corresponding BGC variants. However, tools to rapidly visualize the core gene set and distinguish it from variant-specific tailoring genes (VSTGs) in these BGCs are lacking. Here, the software tool BisCEET (Biosynthetic Cluster Environment Examination Tool) was developed, allowing comparison and visualization of the gene composition of related BGCs, thereby streamlining the identification of VSTGs in uncharacterized BGC variants and strains likely to produce novel NP congeners. The use of BisCEET is exemplified by analyzing bacterial BGCs of staurosporine-like indolocarbazoles and xantholipin-like polyketides, which enabled the identification of numerous apparent BGC variants. We anticipate that BisCEET will become a valuable bioinformatic asset, streamlining the prioritization of BGCs and the cultivation of microbial strains for the discovery of distinct NP variants and novel tailoring enzymes.